COMMENT

EVOLUTION Why do we
enjoy the misfortunes
of others? p.147

DEVELOPMENT CalestousJuma
weighs up a call for a
revolution to end hunger p.148

INFLUENZA Plan announced for

gain-of-function studies on
H7N9 virus p.150

LACKS FAMILY/VIRGINIA DEPT HISTORIC RESOURCES

ENVIRONMENT A road
map for reducing
Chinas emissions p.143

Henrietta Lacks family gather around a historical marker dedicated to her in Virginia in 2011.

Family matters

Kathy L. Hudson and Francis S. Collins discuss how and why the US National
Institutes of Health worked with the family of Henrietta Lacks, the unwitting source
of the HeLa cell line, to craft an agreement for access to HeLa genome data.

n March, two of the most deeply held

values in the medical-research community public data-sharing and respect
for research participants collided when
the genome of the ubiquitous cell line HeLa
was published1 and posted in a public database. Controversy ensued. The full sequence
data could potentially uncover unwanted
information about people whose identity
is widely known: the family of the woman
from whom this immortal line was derived
62years ago, Henrietta Lacks.

So, since March, the US National Institutes

of Health (NIH) in Bethesda, Maryland, has
worked closely with Lacks family. Together,
we have crafted a path that addresses the
familys concerns, including consent and
privacy, while making the HeLa genomic
sequence data available to scientists to
further the familys commitment to biomedical research.
The agreement that we reached goes into
effect this week. We hope that it, and its genesis, will spur broader discussions regarding

consent for future use of biospecimens, with

a goal of fostering true partnerships between
researchers and research participants.

MEDICAL HISTORY

In 1951, physicians at Johns Hopkins Hospital

in Baltimore, Maryland, took a biopsy from
Henrietta Lacks, a 31-year-old African
American woman who had an aggressive
form of cervical cancer. This biospecimen
was taken without her permission or knowledge; US regulations requiring consent
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2013 Macmillan Publishers Limited. All rights reserved

COMMENT
were still decades away. The tissue sample
gave rise to the first human cancer-cell line
that could grow endlessly in culture, called
HeLa. Henrietta died later that year, but her
cells live on. Today, more than 60years later,
scientists around the world use HeLa cells for
research on almost every disease. The story of
Lacks unwitting contribution to science, and
the proud and poignant legacy it left for her
descendants, is told in Rebecca Skloots bestselling book, The Immortal Life of Henrietta
Lacks (Crown, 2010), which is now being
made into a film by Oprah Winfreys production company.
The German research team that in March
this year posted the HeLa genome on openaccess databases available through the
European Bioinformatics Institute and the
NIHs National Center for Biotechnology
Information did not violate any laws or rules.
The action did, however, upset the Lacks
family, and it drew criticism from many
quarters2. The genome of these cells is not
identical to Lacks original genome. The cells
carry the genetic modifications that allowed
them to form a tumour and grow prolifically;
and their passage in cell culture for more
than six decades has led to other structural
anomalies. Nonetheless, the sequence can
reveal certain heritable aspects of Lacks germline DNA, and can thus be used to draw
inferences, admittedly of uncertain significance, about her descendants.
Within days, the European researchers removed the sequence from the public
databases, to allow time for consideration
of alternative approaches. Meanwhile, an
NIH-funded research paper by AndrewAdey
and colleagues on the genome sequence of
a second HeLa line was in press at Nature
(published in this issue; see page 207)3.
Nature mandates that authors of research
papers make their data publicly available
online. Something needed to be done and
in partnership with the Lacks family.

WEIGHING THE OPTIONS

Over the past four months, with help from

Skloot and academic leaders at Johns
Hopkins, we met members of the Lacks
family in Baltimore on three occasions. At
their request, some family members also met
separately with an NIH genetic counsellor
and medical-genetics expert to learn more
about what the data might say about family
members, and the implications of having it
in the public domain.
We talked at length with the family about
the three options available for the full HeLa
sequence data: first, making the sequence
freely available, allowing anyone access at any
time and for any use; second, placing the data
in a controlled-access database, which would
require researchers to apply to the NIH to
use the data in a specific study and to agree
to terms of use defined by a panel including

members of the Lacks family; or third,

withholding the sequence and not making it
available at all for research an option that
the NIH would have had difficulty supporting
or implementing, philosophically and legally.
After much discussion, family members
unanimously favoured the controlled-access
option. This will allow them to be aware of
and have a crucial role in the science that
uses the HeLa genome. The NIH will help to
implement this, but respecting the familys
preferences has required (and will continue to
require) cooperation and patience by many
including scientists, publishers, funders and
scientific societies. The authors and publishers of both genome
papers1,3 have agreed
Nonto submit their data
identifiability
is increasingly for controlled access
(in the same way as for
illusory,
many other non-HeLa
owing to
genome sequences)
technological
through the NIHs
advances.
database of genotypes
and phenotypes (dbGaP; see go.nature.com/
fduced). Likewise, NIH-funded researchers who sequence other HeLa lines will be
expected to deposit their data in the dbGaP.
We hope that scientists whose work is supp
orted by other funders will do the same.
Applications for access to the sequence data
will be rapidly reviewed by a newly formed
HeLa Genome Data Access working group
at the NIH, on which two members of the
Lacks family will serve. We believe that this
plan reflects the true partnership between
the Lacks family and the biomedical-research
community. We also ask that all researchers
who generate or use genomic data from HeLa
cells include in their publications an acknowledgement of the contribution of Lacks and the
continued generosity of her family, such as
that in Adey and colleagues paper3.
Of course, someone could still stitch
together a reasonable representation of the
HeLa genome from the estimated 1,300gigabytes of data already in public databases,
which have been accumulating over the past
25years and the family knows this. The
family is also aware that any lab with the right
equipment, and non-NIH funds, could derive
the full sequence from scratch at any point
and post it on a non-NIH website. However, we urge the research community to act
responsibly and honour the familys wishes.
Downloading the HeLa sequence through
controlled access is the right and respectful
thing to do.
It is important to note, however, that we
are responding to an extraordinary situation
here, not setting a precedent for research
with previously stored, de-identified specimens. The approach we have developed
through working with the Lacks family is
unique because HeLa cells were taken and
used without consent, and gave rise to the

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most widely used human cell line in the

world, and because the family members are
known by name to millions of people.
The furore around HeLa cells has brought
the absence of consent requirements for
some biospecimen research to public attention. Under current US federal guidelines, it
is still possible to use specimens and to generate whole-genome sequencing data without
the knowledge or permission of the person
providing the sample, as long as the biospecimen meets the definition of de-identified
(see go.nature.com/2jrzvz). The administration of President Barack Obama is undertaking fundamental reforms for the protection
of human subjects in research. Among the
factors motivating these reforms is the recognition that non-identifiability is increasingly
illusory, owing to technological advances,
especially in genomics and computing47. In
addition, the relationship between researchers and participants is evolving: seeking
permission emphasizes that participants are
partners, not just subjects.
In July 2011, the US Department of Health
and Human Services issued a notice requesting public comment on how current regulations for protecting participants in research
might be revised to be more effective (see
go.nature.com/LL6es9). Among other questions, the notice sought comment on whether
the department should require consent for
future research using samples, identified or
not. The notice also sought input on the use of
broad consent for unspecified future research
use of specimens. The question assumed that
specimens that were collected before a change
in regulations would be governed by the old
rules. On the basis of those public comments,
the department is preparing a new proposal.
It is fitting, given the priceless contributions that Henrietta Lacks has made
to science and medicine, that her story
is catalysing enduring changes in policy.
These should afford future generations of
research participants the protections and
respect that were not in place during Lacks
lifetime. SEE WORLD VIEW P.123
Kathy L. Hudson is deputy director for
science, outreach and policy at the National
Institutes of Health (NIH) in Bethesda,
Maryland. Francis S. Collins is director of
the NIH.
e-mail: kathy.hudson@nih.gov
1. Landry, J. J. M. et al. Genes Genomes Genet. http://
dx.doi.org/10.1534/g3.113.005777 (2013).
2. Skloot, R. The Immortal Life of Henrietta Lacks,
the Sequel The New York Times (23 March 2013).
3. Adey, A. et al. Nature 500, 207211 (2013).
4. Lin, Z., Owen, A. B., Altman & R. B. Science 305,
183 (2004).
5. Lowrance, W. W. & Collins, F. S. Science 317,
600602 (2007).
6. Gymrek, M., McGuire, A. L., Golan, D., Halperin, E.
& Erlich, Y. Science 339, 321324 (2013).
7. Rodriguez, L. L., Brooks, L. D., Greenberg, J. H. &
Green, E. D. Science 339, 275276 (2013).